Acentralprobleminovariancancerislatediagnosis,whenthe5-yearsurvivalrateplummetstolessthan 50%.Ovariancancersymptomsarevagueandnonspecific,andscreeningisnotgenerallyeffective.Because ovariancancerissodeadly,prophylacticbilateralsalpingo-oophorectomy(BSO)isoftenrecommendedfor womenathighrisk,howeverBSOhasfertilityandhealthconsequences.Also,foralargenumberofwomenat elevatedbutnotextremelyhighrisk,thebestpreventionaction-atthebesttime-isunclear.Itisnowbelieved thatdeadlyovariancancermayactuallystartinthefallopiantubes(FTs),andthatprecancerouscellsmightbe detectablebeforetheyspreadtotheovary.TheFTscanbeexaminedbypassingathinfalloposcopethrougha hysteroscopeandtheostiaoftheFT.Ourlong-termgoalistocreateaneffective,minimal-invasive,and clinicallyreliablemethodtoassessawoman?sFThealthincludingdetectingtheearliestpre-cancerous abnormalities,toguideaphysician?sandpatient?schoiceofappropriatepreventionortreatmentmethods. Detectingsmallpremalignantlesionsischallenging,andwewillemploythreecomplimentarytechniques withpromiseforthistask.Thefirstismultispectralfluorescenceimaging(MFI),whichhaspreviouslybeen showntodifferentiatenormalfromcanceroustissueintheovariesandFT.Thisinstantaneous,intacttissue modalitywillbecombinedwithtwoexvivocellularanalysistechniquesknowntobesensitivetosubtlepre- cancerouschanges.First,ReversePhaseProteinMicroarray(RPPA)measuresfunctionalcellularproteinsin microscopicquantitiesofcells,includinganumberofkeysignalingandbiochemicaleventsthatareknown mediatorsofcanceroustransformation.Second,karyometry,orcomputer-aidedchromatinpatternanalysis, hasbeenshowninseveralorganstocorrelatewithpresenceofearlydiseaseandriskofprogressionto invasivecancer.IthasalsoshownnormalizationofovaryandFTtissueafterchemoprevention,andhas revealedthepresenceofastrongfieldeffectinmanyorgans,ortheabilitytosenseacancerouslesionseveral centimetersawayfromthecellcollectionsite. TheoverallgoalofthisprojectistoshowproofofprincipleofacombinedmethodfordifferentiatingFT samplesfromnormalrisk,highrisk,andovariancancerpatients,andtodevelopamethodthatcanbeusedto collectingadequateFTcellsforanalysis.Thespecificaimsare: Aim1.Examinetissue-bankedandnewly-collectedhistologicalsectionsofFTswithfluorescenceimaging, RPPA,andkaryometrytodevelopanintegratedalgorithmthatstratifiespatientsbasedonpresenceofdisease andasafunctionofknownpatientriskstatus.ExaminethealgorithmasafunctionofspatiallocationintheFT. Aim2:Developafalloposcope,containinganimagingchannelfornavigationandMFIcapability,aswellas acellsamplingchannel.Examineaspirationandwirescrapeoptionsfortheirabilitytocollectadequatecells forRPPAandkaryometryanalysis.